All issues > Volume 53(4); 2010

Original Article

Korean J Pediatr. 2010;53(4):525-531. Published online April 15, 2010.

Apoptosis and upregulation of TNF-α and TRAIL receptor 1 (DR4) in the pathogenesis of food protein-induced enterocolitis syndrome

Jin-Bok JB Hwang¹, Sang Pyo SP Kim², Yu Na YN Kang², Seong-Ryong SR Lee³, Seong-Il SI Suh³, Taeg Kyu TK Kwon³

¹Departments of Pathology, Keimyung University School of Medicine, Daegu, Korea
²Departments of Pathology, Keimyung University School of Medicine, Daegu, Korea
³Institute for Medical Science, Keimyung University School of Medicine, Daegu, Korea

Correspondence Jin-Bok JB Hwang ,Email: pedgi@kmu.ac.kr

Abstract

Purpose
: Expression levels of tumor necrosis factor (TNF)-α expression on the mucosa of the small intestine is increased in patients with villous atrophy in food protein-induced enterocolitis syndrome (FPIES). TNF-α has been reported to induce apoptotic cell death in the epithelial cells. We studied the TNF family and TNF-receptor family apoptosis on the duodenal mucosa to investigate their roles in the pathogenesis of FPIES.
Methods
: Fifteen infants diagnosed as having FPIES using standard oral challenge test and 5 controls were included. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining was performed to identify the apoptotic cell death bodies. Immunohistochemical staining of TNF-α, Fas ligand (FasL) for TNF family and TNF-related apoptosis-including ligand (TRAIL) receptor 1 (DR4), TRAIL receptor 2 (DR5), and Fas for TNF-receptor family were performed to determine the apoptotic mechanisms.
Results
: TUNEL+ was significantly more highly expressed in the duodenal mucosa of FPIES patients than in controls (P = 0.043). TNF-α (P =0.0001) and DR4 (P =0.003) were significantly more highly expressed in FPIES patients than in controls. Expression levels of FasL, Fas, and DR5 were low in both groups and were not significantly different between the 2 groups.
Conclusion
: These results suggest that FPIES pathogenesis is induced by apoptosis, and that TNF-α expression and DR4 pathway may have an important role in apoptosis.

Keywords :Food protein-induced enterocolitis syndrome, Etiology, Apoptosis, Tumor necrosis factor-alpha, TNF-related apoptosis-including ligand receptor 1